Description (adapted for the investigator's abstract): Enthusiasm over anti-melanoma immunization strategies has been heightened by the recent documentation of objective tumor regressions following peptide immunization. Future vaccination trials in melanoma will focus on delivery of multiple peptides or full-length antigenic cDNA in an effort to increase the frequency and duration of clinical responses. Similarly, interest in polynucleotide immunization is rapidly growing with numerous demonstrations of efficacy in animal models of infectious diseases and cancer, including nonhuman primate trials. However, the initial trials of polynucleotide vaccines in humans have produced more modest immune responses, suggesting the importance of incorporating augmentation strategies into second generation trials of modality. We believe that such augmentation strategies can only be adequately addressed in well-designed human clinical trials. Thus, our current proposal has the following specific aims: 1) To carry out a phase I dose escalation trial of polynucleotide immunization with plasmid DNA encoding MART-1 (melanoma antigen recognized by T-cells-1) in patients with resected melanoma at significant risk for relapse; 2) To carry out a phase I doe escalation trial of intramuscular injection of plasmid DNA encoding human interleukin-12 in patients with advanced solid malignancies; 3) To carry out a pilot study of sequential immunization with plasmid DNA encoding modified gp100 and co-administered ALVAC-gp100 with ALVAC-GM-CSF in patients with resected melanoma at significant risk for relapse; and 4) To carry out a pilot study of IL-12encoding plasmid co-administered to augment the immune response to DNA plasmids encoding MART-1 and HbsAg in patients with resected melanoma at significant risk for relapse. In all three of the proposed tumor antigen vaccine trial, patients will be monitored by extensive laboratory studies to access both antibody and T cell antigen-specific immune responses induced by experimental vaccines.